Registration Dossier
Registration Dossier
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EC number: 701-175-2 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Repeated dose toxicity: oral
Administrative data
- Endpoint:
- repeated dose toxicity: oral, other
- Remarks:
- Gastroplus modelling of repeated oral exposure to rats for 90 days
- Type of information:
- other: In silico predictive model
- Adequacy of study:
- supporting study
- Study period:
- April-July 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Justification for type of information:
- Information on oral absorption and other major pharmacokinetic parameters is provided in support of data waiving arguments for in vitro micronucleus assay and repeat dose oral toxicity studies
Data source
Materials and methods
- Principles of method if other than guideline:
- For the predictions of Fa%, F%, Css, and AUC 0-2160 hr of the representative major components of PRIMENE 81-R following 90-day repeated dietary exposures in rats, a PBPK model was utilized in GastroPlus (version 9.7). This PBPK model contains 13 compartments (lung, adipose, muscle, liver, spleen, heart, brain, kidney, skin, reproductive organs, red marrow, yellow marrow, and the rest of the body). In this PBPK simulation, the oral dose formulation type was defined to be a suspension (equivalent to the dietary type in the defined PBPK model) with particle size of 25 μm mean radius
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Specific details on test material used for the study:
- Not applicable - method is an in silico predictive model
Test animals
- Species:
- other: Not applicable - method is an in silico predictive model
- Strain:
- not specified
- Remarks:
- In silico rat model
- Details on species / strain selection:
- Not applicable - report is an in silico rat model of gastric absorption
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- Not applicable - report is an in silico rat model of gastric absorption
Administration / exposure
- Route of administration:
- oral: feed
- Details on route of administration:
- Simulation of dietary administration
- Vehicle:
- other: Not applicable - report is an in silico rat model of gastric absorption
- Details on oral exposure:
- Simulated oral dietary exposure for a period of 90 Days
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- Simulated oral dietary exposurefor a period of 90 days
- Frequency of treatment:
- Simulated dietary exposure for a period of 90 days
- No. of animals per sex per dose:
- Not applicable
- Details on study design:
- In silico predictive model of gastric absorption
- Positive control:
- Not applicable
Results and discussion
Results of examinations
- Clinical signs:
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
Applicant's summary and conclusion
- Conclusions:
- PRIMENE™ 81-R (Amines, C10-C14-tert-Alkyl) is a mixture containing major components with alkyl carbon number ranged from C10 to C14. Experimental data on oral absorption in rats either from single or repeated oral exposures (such as repeated 90-day dietary exposure) is not available for this mixture. Therefore, the oral bioavailability, other major pharmacokinetic parameters, and metabolic clearance data of the major representative 20 components of the mixture were estimated via the widely accepted QSAR programs, ADMET predictor (v9.5, Simulations Plus Inc, Lancaster, CA, USA), and GastroPlus (v9.7, Simulations Plus Inc, Lancaster, CA, USA).
Using the parameters for a repeated 90-day oral dietary exposure to a fed rat (0.25 kg) at dose level of 107 mg/kg/day (mkd), the predicted fractional absorption (Fa%), bioavailability (F%), and maximum steady-state plasma concentration (Css ), area under curve (AUC) values, and rat liver microsomal clearance (CYP-RLM-CLint) of the representative 20 components by GastroPlus were determined.
Overall, the predicted Fa%, F%, Css, AUC, and CYP-RLM-CLint for these major components were in the ranges of 97.60-99.81%, 16.10-34.97%, 0.646-1.092 μg/mL, 493-999 μg.h/mL, and 196.602-435.343 μl/min/mg RLM protein, respectively.
According to the predicted values of Fa%, F%, Css, and AUC, all these representative components of PRIMENE 81-R are bioavailable in rats, and the predicted CYP-RLM-CLint values indicate that all these representative components can be metabolized via cytochrome p450 (CYP). The predicted plasma time-courses of the representative components indicated no apparent bioaccumulation of any of the representative major components of PRIMENE 81-R upon repeated-day exposures at the dose level of 107 mkd. - Executive summary:
PRIMENE™ 81-R (Amines, C10-C14-tert-Alkyl) is a mixture containing major components with alkyl carbon number ranged from C10 to C14. Experimental data on oral absorption in rats either from single or repeated oral exposures (such as repeated 90-day dietary exposure) is not available for this mixture. Therefore, the oral bioavailability, other major pharmacokinetic parameters, and metabolic clearance data of the major representative 20 components of the mixture were estimated via the widely accepted QSAR programs, ADMET predictor (v9.5, Simulations Plus Inc, Lancaster, CA, USA), and GastroPlus (v9.7, Simulations Plus Inc, Lancaster, CA, USA).
Using the parameters for a repeated 90-day oral dietary exposure to a fed rat (0.25 kg) at dose level of 107 mg/kg/day (mkd), the predicted fractional absorption (Fa%), bioavailability (F%), and maximum steady-state plasma concentration (Css ), area under curve (AUC) values, and rat liver microsomal clearance (CYP-RLM-CLint) of the representative 20 components by GastroPlus were determined.
Overall, the predicted Fa%, F%, Css, AUC, and CYP-RLM-CLint for these major components were in the ranges of 97.60-99.81%, 16.10-34.97%, 0.646-1.092 μg/mL, 493-999 μg.h/mL, and 196.602-435.343 μl/min/mg RLM protein, respectively.
According to the predicted values of Fa%, F%, Css, and AUC, all these representative components of PRIMENE 81-R are bioavailable in rats, and the predicted CYP-RLM-CLint values indicate that all these representative components can be metabolized via cytochrome p450 (CYP). The predicted plasma time-courses of the representative components indicated no apparent bioaccumulation of any of the representative major components of PRIMENE 81-R upon repeated-day exposures at the dose level of 107 mkd.
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